Controlling the exotic diseases: 2. Nursing management.

Advance planning can facilitate the care of a patient with an exotic disease who is admitted to a hospital that lacks facilities for high-security isolation. The Department of National Health and Welfare contingency plan for dealing with such patients lacks specific information in a number of areas of medical care, as described in this paper. Consideration must be given to the number of personnel trained and readied for employment, the criteria for selection and special preparation. The protective clothing generally used for hospital isolation procedures is inadequate. Several types of special clothing, including a respirator, are available for total protection of personnel; the clothing may be uncomfortable when worn for long periods, and does restrict movement, vision and communication. All persons entering the isolation suite must change into fully protective clothing, and double layers of clothing are required for direct patient care. All personnel must shower and change before leaving the isolation suite. Suitable facilities for dressing and showering, together with entry and exit routines, must be considered. Hand washing, daily cleaning procedures and disposal of liquid and solid wastes all require special procedures. The social and psychologic problems of patients and their families must also be considered. Preplanning is required to decrease the risks involved in monitoring vital signs and implementing emergency procedures requiring contact with the patient''s blood.     

Clinical involvement of Aeromonas hydrophila.

Aeromonas hydrophila has for some time been regarded as an opportunistic pathogen in hosts with impaired local or general defence mechanisms. Infections in such individuals are generally severe. The organism is also being isolated with increasing frequency throughout the world from a variety of focal and systemic infections of varying severity in persons that are apparently immunologically normal. Most commonly it causes acute diarrheal disease by producing an enterotoxin. Thus the organism appears to have greater clinical significance that was hitherto suspected. The organism has been infrequently reported from humans in Canada, but its correct laboratory identification, together with increased awareness that it can contribute to illness, will undoubtedly lead to more reports of its isolation in Canada.     

Lassa fever,Marburg and Ebola virus diseases and other exotic diseases: is there a risk to Canada?

There are seven exotic diseases of concern; three of these, the most unpredictable and least understood, are Lassa fever, Marburg virus disease and Ebola virus disease. In this article the epidemiologic aspects of these diseases are discussed, with particular emphasis on exportation from their indigenous areas in Africa and on the occurrence of secondary cases. Any of these conditions could be brought into Canada either by aeromedical evacuation or inadvertently. Between 1972 and 1978 there were seven occasions when Canada could have been involved with handling cases of Lassa fever. The Government of Canada has purchased several containment bed and transit isolators. These units, with filtered air under negative pressure, accommodate infectious patients being transported and cared for without contaminating medical attendants or the environment.     

Current Concepts in Dermatology: III. The Use of Radiotherapy and Corticosteroids

The use of ionizing radiation and corticosteroids is discussed, in this third and final part of a review of diseases of the skin. Radiation is being used less extensively because superior methods of treatment are available for many conditions which formerly were frequently treated by this modality. The concept of applying the radiation at the level of the basic pathologic process has been developed into clinical practice by the use of generators which can produce very soft (or superficial) ionizing radiation. Topical or systemic corticosteroids do not cure skin diseases but produce dramatic suppression of signs and symptoms. For best results consideration must be given to the diagnosis, the natural history of the disease to be treated, the method of administration and a search for possible contraindications to the use of these steroids. Basic dermatological principles (removal of offending agents, bland soothing applications, sedation, etc.) must be adhered to. The corticosteroids are not a panacea in the treatment of skin disease.     

Human transfer factor. II. Clinical results with the large pool transfer factor

21 patients with diseases due to immunological causes were treated 6 times at an interval of four weeks by administering 5 E TF or 1 E TF each per 10 kg of body weight. TF consisted of 5 different large pool TF charges of 420 to 822 buffy-coats of fresh stored whole blood. Clinical and immunological investigations as well as biochemical ones in the laboratory were made before and after treatment. Large pool TF is clinically effective in 9 from 18 patients and immunologically in 16 from 18 patients. There is a greater effect in immunodeficiencies than in autoimmune diseases. TF is not able to remove the defect for a long time. Repeated administrations are required. TF therapy may be regarded as a substitution therapy. At first, the intervals have to be chosen according to clinical parameters (recidive of the disease or crisis respectively). There is a good compatibility of TF. Side-effects could not be observed. The frequent immunological conversions after score evaluation indicate, however, that in comparison to the clinical appearance the course of the disease must be seen to be much more complex than it can be expressed by in vitro correlates of immunological responses. Statistically ensured correlations of single tests concerning the clinical course could also not be found. Large pool TF provides favourable conditions for controlled therapy trials in order to elucidate those findings of therapy which hitherto had been a subject of controversy (e.g. autoimmune diseases, tumours).     

Isolation and culture of bovine oviductal epithelial cells for use in the anatomy and physiology laboratory and undergraduate research

This article presents methods for the isolation and culture of epithelial cells from the bovine oviduct for use in both research and the teaching laboratory and provides examples of ways that an oviductal cell culture can be incorporated into an undergraduate research program. Cow reproductive tracts are readily available from area butchers, and the procedure for isolation of the epithelium is simple and inexpensive. The cells can be observed immediately after isolation or can be cultured for up to 72 h under simple conditions for observation over several days. For experimental use, epithelial cells are cultured in standard cell culture medium, where they continue to divide and actively secrete substances into the medium. The ease with which the tissue can be collected and cells isolated makes the oviductal epithelium ideal for use in both the teaching laboratory and research projects in which undergraduates serve as investigators.     

Parasitic disease in humans: the extent in Canada.

Much is being said, often dramatically, about the potential hazards of parasitic diseases in Canada, but little or no attempt has been made to determine the true extent of the problem. Indigenous parasite pathogens are recognized in resident Canadians, and pathogens are acquired by travellers abroad or reported from immigrants. The role of each of these categories is important in the characterization of the problem of parasitic diseases in Canada. From data provided by provincial laboratories and hospitals it is estimated that 1 person in 1000 will spend 1 day per year in hospital because of intestinal parasites, and 1 in 100 each year will have a diagnosis of intestinal parasitic infection made from examination of a stool sample.     

Syndromic surveillance for influenzalike illness

Emergency department data are currently being used by several syndromic surveillance systems to identify outbreaks of natural or man-made illnesses, and preliminary results suggest that regular outbreaks might be detected earlier with such data than with traditional reporting. This article summarizes a retrospective study of 5 influenza seasons in Ottawa,Canada; time-series analysis was used to look for an association between consultation to the emergency department for influenzalike illness and the isolation of influenza virus in the community. The population studied included both children and adults consulting to 3 local hospitals. In 4 seasons, visits to the emergency department involving children younger than 5 years consulting mainly for fever and for respiratory symptoms peaked 1 to 4 weeks before the isolation of influenza virus in the community. If monitored regularly for the presence of key symptoms, pediatric hospitals might be efficient and cost-effective sentinels of influenza and of other infectious diseases.     

AIDS: acquired immunodeficiency syndrome.

Acquired immunodeficiency syndrome, or AIDS, is a new illness that occurs in previously healthy individuals. It is characterized by immunodeficiency, opportunistic infections and unusual malignant diseases. Life-threatening single or multiple infections with viruses, mycobacteria, fungi or protozoa are common. A rare neoplasm, Kaposi''s sarcoma, has developed in approximately one third of patients with AIDS. More than 800 cases of AIDS have been reported in North America, over 24 of them in Canada. The majority of patients are male homosexuals, although AIDS has also developed in abusers of intravenously administered drugs, Haitian immigrants, individuals with hemophilia, recipients of blood transfusions, prostitutes, and infants, spouses and partners of patients with AIDS. The cause of AIDS is unknown, but the features are consistent with an infectious process. Early diagnosis can be difficult owing to the nonspecific symptoms and signs of the infections and malignant diseases. Therefore, vigilance by physicians is of utmost importance.     

Medico-genetic study of isolates in Uzbekistan. IV. Clinico-biochemical diagnosis of hereditary diseases]

An exhaustive clinico-biochemical examination of the population of two kishlaks of the Samarkand Region, viz. Karakent (210 persons) and Ishan (248 persons) was carried out. The program of this examination permitted to exclude over 160 forms of hereditary pathology. A total of 45 persons affected with diseases belonging to 12 nosological forms were revealed in the course of the examination. Among the diseases observed only 5 are hereditary sensu stricto, viz. myoclonus-epilepsy, Bonevi-Ulrich's syndrome, imperfect osteogenesis, pigment choreoretinite and Down's syndrome, others belong to diseases with a pronounced hereditary predisposition. The main part of this group comprises neuro-psychic diseases, such as non-differentiated olygophreny (5.0%), epilepsy (1.3%), schizophreny; many of these cases have a familial character, particularly in Karakent. Besides the persons suffering from diseases, 20 heterozygous carriers of beta-thalassemia and 17 heterozygous carriers of G6PD-deficiency were discovered in the kishlaks examined. On the whole the frequency of the diseases revealed did not exceed the level in the general population. Despite the different degree of isolation of the kishlaks examined (Karakent is isolated on a religious basis, F = 0.0064; while Ishan is a desintagrated isolate, F = = 0.0014), no substantial differences between them in the distribution of pathological phenomena were observed. On the basis of the experience of this expedition recomendations are proposed concerning the origination and accomplishment of medico-genetic expeditions. A scheme is proposed for the performance of medico-genetic examination through several stages. The first stage in the composition of tentative maps of the distribution of hereditary diseases within a region on the basis of the information obtained from the medical personnel and from the examination of the documents of district and regional hospitals. Subsequently the primary information is specified, the regions to be examined are determined, as well as concrete tasks and the staff of the expedition. The conclusive stage is the medico-genetic examination proper, including clinical, biochemical, immunological and cytogenetic diagnoses of hereditary pathological phenomena. The place of the disposition is a village or a district hospital. More complicated laboratory studies should be performed on the basis of the institution by which the expedition is formed. The results obtained by such expeditions would be important for the investigation of the problems of genogeography, for the discovery of new forms of mutant alleles, for the investigation of the causes and the conditions of the formation of the definite populational structure, of clinical polymorphism of human hereditary diseases.     

Preparation of tissue polypeptide antigen (TPA) from sera pools of cancer patients.

TPA is a tumor marker characteristic of general cellular proliferation. High serum levels are found in patients with tumor progression. With the aim of bettering the clinical use, the authors have isolated TPA in purer form, in order to develop, in the future, a more specific immunoenzymatic method based on unlabeled antipeptide antibodies. A simple method for the isolation of small amounts of tissue polypeptide antigen (TPA) from the sera of patients suffering from neoplastic diseases is described. The procedure takes advantage of the availability of commercial anti-TPA coated beads; sera pools with high levels of antigen are allowed to react with such beads, then the antibody-antigen complex is dissociated by drastic changes of pH or molarity, and TPA recovered. Such TPA preparations contain low amounts of extraneous proteins, and thus can be utilized in immunoenzymatic tests, or in laboratory investigations.     

Cultivation of the mosquito Culex pipiens pipiens f. molestus (Diptera, Culicidae) without blood feeding

Optimal photoperiod and temperature conditions for rearing of the mosquito Culex pipiens pipiens f. molestus without blood feeding (through autogenous eggs) were experimentally substantiated. This method may be used in order to obtain relatively small quantities of mosquitoes or for preservation of a laboratory colony. Optimal conditions of rearing are the short-day photoperiod (12 h of light per day) at 20 degrees C, when 87 % of the females produce autogenous eggs rafts consisting of 52 eggs on the average. It should be emphasized that larval food must be adequate and abundant, because the quality and quantity of it has a pronounced effect on the autogeny rate.     

LABORATORY EXPERIMENTS ON SPECIATION: WHAT HAVE WE LEARNED IN 40 YEARS?

We integrate experimental studies attempting to duplicate all or part of the speciation process under controlled laboratory conditions and ask what general conclusions can be made concerning the major models of speciation. Strong support is found for the evolution of reproductive isolation via pleiotropy and/or genetic hitchhiking with or without allopatry. Little or no support is found for the bottleneck and reinforcement models of speciation. We conclude that the role of geographical separation in generating allopatry (i.e., zero gene flow induced by spatial isolation) has been overemphasized in the past, whereas its role in generating diminished gene flow in combination with strong, discontinuous, and multifarious divergent selection, has been largely unappreciated.     

Biomarker responses in human populations: towards a worldwide map.

The discipline of epidemiology studies the determinants of diseases in human populations, identifies causes, determines outcomes and develops prevention strategies. Traditional epidemiology is most useful for studies of acute, relatively common diseases with short incubation periods but less so for studies of chronic low incidence diseases with long incubation periods. Molecular epidemiology, which employs biological responses or biomarkers as surrogates of exposures or effects, can help with the latter. For this reason, there is a great interest in developing and validating biomarkers. DNA damage underlies an important group of chronic diseases with long incubation periods, i.e., cancer. Biomarkers may measure the exposures that induce the DNA damage, the damage itself, or individual susceptibility to damage. Before they can be used for human population research, however, these measures must be validated. Biomarker validation critically depends on field studies. This is accomplished through transitional epidemiological studies that 'bridge the gap' between laboratory and field. Transitional epidemiological studies are of three varieties: (i) Developmental, (ii) Characterization, and (iii) Applied. Biomarkers are the dependent variables in transitional studies. An international network of laboratories for human population monitoring requires yet another dimension for validation, i.e., the comparability of results among laboratories must be determined. This will be achieved by sample sharing projects, with workshops to compare results. Only then can results in one population be compared with results in another. Interlaboratory standardization of assays for biomarkers validated by transitional studies will have far-reaching benefits. It will allow development of worldwide databases of background values for the various biomarkers-or biomarker maps. This, in turn, will facilitate problem identification and eventually constitute the baselines for area-specific population monitoring. Biomarker databases so developed can be compared with worldwide databases for cancer and heritable diseases, validating the former as statistical surrogates of the latter.     

Cardiovascular disease mortality in Canada.

During the past two decades approximately one half of all deaths in Canada were due to cardiovascular diseases. Ischemic heart disease and cerebrovascular disease caused more than 60% and 20% of those deaths respectively. The mortality rates for ischemic heart disease in males increased slightly until 1965 and then dropped substantially, whereas the rates for females, which were declining at least since the early 1960s, accelerated in their decline. As a consequence, the rates for males remain almost twice as high as those for females. The reductions were initially observed in males 25 to 34 years old and in all age groups of females, but became apparent in a wider range of ages in the second period reviewed (1969 through 1977). The mortality of cerebrovascular disease has gradually diminished for both sexes since the 1950s, but the decline has been more pronounced among females, who originally had the higher rate. Marked geographic differences in mortality rates still exist in Canada despite the decline in death rates for both ischemic heart disease and cerebrovascular disease in all regions of the country. Surprising regional differences in times of onset of these declines have been demonstrated. For ischemic heart disease Ontario maintains the highest and the Prairies the lowest mortality rates. Quebec, despite a sustained decline, still ranks third, while the Pacific region shows the second-lowest rates in the country. The Atlantic region showed the lowest rates of decline in the period reviewed. The reduction in the mortality of ischemic heart disease in Canada (16.4% between 1969 and 1977) must be considered real for a variety of reasons. Direct evidence is not available to elucidate whether the reduction is the consequence of reduced incidence, increased survival or a combination of the two factors. The potential role of various factors that may have contributed to this decline is briefly discussed in this article.     

FORGE Canada Consortium: Outcomes of a 2-Year National Rare-Disease Gene-Discovery Project

Inherited monogenic disease has an enormous impact on the well-being of children and their families. Over half of the children living with one of these conditions are without a molecular diagnosis because of the rarity of the disease, the marked clinical heterogeneity, and the reality that there are thousands of rare diseases for which causative mutations have yet to be identified. It is in this context that in 2010 a Canadian consortium was formed to rapidly identify mutations causing a wide spectrum of pediatric-onset rare diseases by using whole-exome sequencing. The FORGE (Finding of Rare Disease Genes) Canada Consortium brought together clinicians and scientists from 21 genetics centers and three science and technology innovation centers from across Canada. From nation-wide requests for proposals, 264 disorders were selected for study from the 371 submitted; disease-causing variants (including in 67 genes not previously associated with human disease; 41 of these have been genetically or functionally validated, and 26 are currently under study) were identified for 146 disorders over a 2-year period. Here, we present our experience with four strategies employed for gene discovery and discuss FORGE’s impact in a number of realms, from clinical diagnostics to the broadening of the phenotypic spectrum of many diseases to the biological insight gained into both disease states and normal human development. Lastly, on the basis of this experience, we discuss the way forward for rare-disease genetic discovery both in Canada and internationally.     

The Occurrence and Pathogenicity of Cylindrocarpon, Cylindrocladium and Fusarium on Calluna vulgaris and Erica spp. in England and Scotland

Cylindrocarpon, Cylindrocladium and Fusarium spp. were often isolated from the woody roots, stem-base and lower foliage of diseased container-grown Calluna vulgaris and Erica spp. plants collected from English and Scottish nurseries. The highest isolation frequencies were obtained for Cylindrocarpon destructans, Cylindrocladium scoparium, Cylindrocladium ilicicola. Fusarium tricinctum, Fusarium avenaceum and Fusarium sporotrichioides . Isolations of these fungi were made more frequently from diseased plants that were at least 1-year-old. The percentage incidence of Cylindrocarpon, Cylindrocladium and Fusarium spp. did not differ between Scottish and English nurseries. Cylindrocarpon destructans. Cylindrocladium ilicicola and C. scoparium were more pathogenic to rooted C. vulgaris cuttings than F. tricinctum. F. avenaceum or F. sporotrichioides in laboratory and glasshouse tests. The high isolation frequency of Cylindrocarpon. Cylindrocladium and Fusarium spp., and their pathogenicity in tests, suggests that these fungi are involved in root, stem-base and lower foliage diseases in crops of C. vulgaris and Erica spp. The importance of these findings for the integrated control of diseases on ericaceous plant nurseries is discussed.     

European field collections and Canadian releases ofCeranthia samarensis (Dipt.: Tachinidae), a parasitoid of the gypsy moth

A programme to collect, import and release into Canada the gypsy moth parasitoid,Ceranthia samarensis (Diptera: Tachinidae) is described. The parasitoid's potential for biological control in Canada is also discussed. The parasitoid was collected in Europe by exposing experimental gypsy moth larvae in areas where local gypsy moth populations were at low densities. Following field exposure, the host larvae were returned to the laboratory and parasitoids reared from them. This technique has shown thatC. samarensis is the suffers 7–16% hyperparasitism. From 83–90% of theC. samarensis typically enter diapause as pharate adults within the puparia. Laboratory tests of post-exposure host rearing conditions indicate that constant temperatures disrupt the normal parasitoid diapause and that this effect can not be offset by use of either static long or short photoperiods or natural daylengths. Shipping and cold-storage procedures for puparia are described. Post-storage time to emergence of adultC. samarensis decreased with longer cold storage periods and with higher post-storage incubation temperatures. Emergence requires 112 degree-days above a threshold of 8°C after a period of at least 8 months cold storage. Releases of adultC. samarensis into field cages at four locations in southern Ontario are documented. While dissection of host larvae from the field cages has failed so far to demonstrate evidence of parasitism, we remain hopeful that some establishment of the parasitoid has occurred.      

Receptor-based assays in screening for biologically active substances.

Molecular biology has identified new receptors and ligands which are deregulated in diseases such as cancer and autoimmune conditions and which provide rational targets for therapeutic intervention. Advances in instrumentation and methodology make it possible to screen large numbers of samples in simple receptor-ligand binding assays in the search for drug candidates. Caution must be exercised in the interpretation of data derived from such assays. This is particularly pertinent to the recently characterized receptors, such as the cytokine receptors, as we do not fully understand the relationship between the receptor type and the linkage of receptors to the appropriate or inappropriate second messenger systems that are used in the experimental screening protocols and the disease state.     

Use of Risk Analysis for Screening Weed Biocontrol Agents: Altica carduorum Guer. (Coleoptera: Chrysomelidae) from China as a Biocontrol Agent of Cirsium arvense (L.) Scop. in North America

Candidate weed biocontrol agents must be screened to exclude those that could threaten desirable plants . Traditionally , this has been done by rejecting species that develop on economically important plants in laboratory no - choice tests . However , because congeneric plants often support development in these tests , even when they are not utilized in nature , the tests do not meet legislated requirements for rare plant species or the increasing public concern for native plants . Plant suitability for larval development is a poor predictor of host range because insects use a sequence of steps in which the early steps , such as host finding and acceptance for oviposition , tend to be stronger than the later ones , such as suitability for development . This study is a trial of a new approach to screening insects as weed biocontrol agents that uses risk analysis to quantify the suitability of a plant as a host on the basis of inset performance at various stages in its life cycle . The insects used for the study was a NW Chinese biotype of the leaf beetle , Altica carduorum, which in terms of climate adaptation and damage it inflicts on the weedy thistle Cirsium arvense, is a promising biocontrol agent for Canada . However , its ability to develop on all North American Cirsium spp . in laboratory no - choice tests currently excludes its release . We show by risk and factor analyses , with five sequential host - selection parameters , that the suitability of these thistles to A. carduorum is so low that the beetle would not jeopardize the continued existence of rare native thistles , so its release should not be a problem .